Syntheses of bicyclo[3.1.0]hexane nucleosides bearing a seven-member diazepinone aglycon were proposed to develop novel inhibitors of cytidine deaminase. To investigate the conformational requirements of the sugar moiety for potent inhibition of CDA, we built the 1,3-diazepin-2-one aglycon on stable bicyclo[3.1.0]hexane scaffolds locked in the extreme North and South conformations of the pseudo-rotational cycle. Together with a flexible inhibitor built on a simple cyclopentane pseudogar, these derivatives were evaluated for their ability to inhibit the deamination reaction. Based on the crystal structure of human CDA with the bound diazepinone riboside, we concluded, that the carbocyclic inhibitor locked in the southern hemisphere should be a better inhibitor for CDA, than its northern antipode. The biological studies supported such conclusion but indicated that the flexible analogue was 100-fold more potent than the preferred southern locked derivative (Nucleic Acids Symposium Series No. 52, 2008, 659-660).